The broad objectives of his proposal are 1) to understand how viruses cause neoplastic transformation, and 2) to understand regulation of viral gene expression in animal cells. The specific objective is a detaild, molecular analysis of Simian Virus 40 (SV40), its development in permissive cells, and transformation of nonpermissive cells by use of variant viruses with deleted or rearranged genomes. We have recently cloned SV40 deletion mutants, lacking specific segments of DNA. We propose to use these to determine the number of SV40 cistrons by complementation; to determine the limits of individual genes by cmplementin various deletion mutants with ts mutants; to determine which genes are needed for viral DNA replication, which code for early viral proteins and viral structural proteins, which are needed for transformation of cells in culture, and for stimulation of host DNA synthesis. In related studies, mechanisms of SV40 transcription will be explored by using SV40 variants containing deleted and/or rearranged segments of DNA.